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| Pàgina inicial > Articles > Articles publicats > TUNAR lncRNA Encodes a Microprotein that Regulates Neural Differentiation and Neurite Formation by Modulating Calcium Dynamics |
(Institut d'Investigació Biomèdica Sant Pau) (Max Delbrück Center) (Vall d'Hebron Institut d'Oncologia) (Centro Nacional de Investigaciones Oncológicas) (Institut d'Investigació Biomèdica Sant Pau) (Vall d'Hebron Institut d'Oncologia)| Data: | 2021 |
| Resum: | Long noncoding RNAs (lncRNAs) are regulatory molecules which have been traditionally considered as "non-coding". Strikingly, recent evidence has demonstrated that many non-coding regions, including lncRNAs, do in fact contain small-open reading frames that code for small proteins that have been called microproteins. Only a few of them have been characterized so far, but they display key functions in a wide variety of cellular processes. Here, we show that TUNAR lncRNA encodes an evolutionarily conserved microprotein expressed in the nervous system that we have named pTUNAR. pTUNAR deficiency in mouse embryonic stem cells improves their differentiation potential towards neural lineage both in vitro and in vivo. Conversely, pTUNAR overexpression impairs neuronal differentiation by reduced neurite formation in different model systems. At the subcellular level, pTUNAR is a transmembrane protein that localizes in the endoplasmic reticulum and interacts with the calcium transporter SERCA2. pTUNAR overexpression reduces cytoplasmatic calcium, consistent with a possible role of pTUNAR as an activator of SERCA2. Altogether, our results suggest that our newly discovered microprotein has an important role in neural differentiation and neurite formation through the regulation of intracellular calcium. From a more general point of view, our results provide a proof of concept of the role of lncRNAs-encoded microproteins in neural differentiation. |
| Ajuts: | Agencia Estatal de Investigación RTI2018-102046-B-I00 Agencia Estatal de Investigación SAF2017-88019-C3-1R Agencia Estatal de Investigación PID2020-116927RB-C21 Agencia Estatal de Investigación PGC2018-094091-B-I00 Agencia Estatal de Investigación RTI2018-095580-A-I00 Agencia Estatal de Investigación RYC-2017-23486 Ministerio de Economía y Competitividad SAF2015-69413-R Ministerio de Economía y Competitividad RYC-2013-14747 "la Caixa" Foundation HR18-00256 |
| Nota: | Altres ajuts: Asociación Española Contra el Cancer (AECC), Cellex Foundation, Mutua Madrileña Foundation. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Licroproteins ; Licropeptides ; Sorf encoded peptides ; TUNAR ; Neural differentiation ; Neurite formation ; Calcium ; Long non-coding RNAs |
| Publicat a: | Frontiers in Cell and Developmental Biology, Vol. 9 (31 2021) , p. 747667, ISSN 2296-634X |
